Chronic depression is a common condition and a major public health problem which has traditionally been thought to be treatment resistant. Recent studies by others have suggested that chronic depressives may have attenuated forms of affective disorders and respond to antidepressant medications. Our own pilot data suggest that chronic depression 1) may be chronically moderate-severe in intensity, 2) often has been treated with psychotherapy but infrequently with adequate drug therapy and 3) appears to respond on substantial rates to the tricyclic antidepressant, imipramine (IMI). The aims of the current proposal are to (1) test the efficacy of a standard tricyclic antidepressant, imipramine (IMI), for treatment of outpatients with primary, early onset, chronic depression, using an eight week, randomized, double-blind, placebo controlled trial, (2) to ascertain clinical factors which predict favorable IMI response in this population, and (3) to determine what percentage of chronic depressives who recover on IMI will remain well during an additional 18 weeks of IMI continuation therapy. The study will be performed as a collaboration involving the outpatient clinics of the New York Hospital and Maine Medical Center. The directors of both of these clinics are co-investigators in the study. Careful baseline measurements of symptoms, severity, family history of psychiatric illness, personality characteristics and social functioning will be done to gather data pertinent to systematic classification of patients with early onset chronic depression, and to develop a profile of clinical characteristics predictive of IMI response. IMI will be given in a dose of up to 300mg a day. Symptoms, severity and side effects will be assessed by blind raters semi-weekly during the double-blind period. Monthly visits during the continuation trial will be held to assess the occurrence of relapse. The significance of the proposed research is that the role of tricyclic antidepressants such as IMI will be clarified and indications for use may be better specified. If such treatment is successful in chronic depression, a major public health advance will be achieved.